Four hundred and sixty (460) subjects will be enrolled nationwide over a 6 month period Ten (10) at the University of Pennsylvania. This is a phase II, randomized, partially placebo-controlled, 4-arm trial comparing amprenavir(AAV) in a single PI regimen versus APV in combo with saquinavir soft-gel=caps (SQV sqc), indinavir (IDV) or nelfinavir (NFV) in HIV infected subjects currently failing IDV ritonavir (RTV). SQV or NFV as pat of a single or dual protease inhibitor regimen as evidenced by plasma HIV-1 RNA concentration of >=1,000 copus/ml. The primary objectives: 1) to compare the proportion of subjects achieving a plasma HIV-1 RNA concentration below 200 copies/ml across the study arms at 24 weeks as assessed by the Roche Ultra Sensitive Assay; 2) to compare the time to quantifiable viremia across the study arms; 3) to compare safety and tolerance across the study arms.